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Elevated blood remnant cholesterol and triglycerides are causally related to the risks of cardiometabolic multimorbidity
Open accessAbstract
The connection between triglyceride-rich lipoproteins and cardiometabolic multimorbidity, characterized by the concurrence of at least two of type 2 diabetes, ischemic heart disease, and stroke, has not been definitively established. We aim to examine the prospective associations between serum remnant cholesterol, triglycerides, and the risks of progression from first cardiometabolic disease to multimorbidity via multistate modeling in the UK Biobank. We also evaluate the causality of these associations via Mendelian randomization using 13 biologically relevant SNPs as the genetic instruments. Here we show that elevated remnant cholesterol and triglycerides are significantly associated with gradually higher risks of cardiometabolic multimorbidity, particularly the progression of ischemic heart disease to the multimorbidity of ischemic heart disease and type 2 diabetes. These results advocate for effective management of remnant cholesterol and triglycerides as a potential strategy in mitigating the risks of cardiometabolic multimorbidity.
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“Observational cohorts demonstrate that higher TG and remnant cholesterol predict cardiovascular events independently of LDL-C, while Mendelian randomization analyses confirm a causal relationship between lifelong TRL elevation and ASCVD.”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [58]
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Li, Y., Zou, Z., Yi, S., Yang, Y., Yuan, G., & Xu, J. (2026) · PLoS ONE · doi:10.1371/journal.pone.0350895
Self-citationWu, X.-F., S, C., Zhang, Y.-C., Liu, S., Yan, B., & Li, X. G. (2026) · BMC Cardiovascular Disorders · doi:10.1186/s12872-026-06008-z
Zhou, Q., Liu, M., Wang, L., Wang, P., Qin, Y., Zhao, M., Wanyan, T., Yu, J., Wan, Y., Zhang, Q. X., et al. (2026) · Frontiers in Nutrition · doi:10.3389/fnut.2026.1864976
Tang, S., & Tao, Y. (2026) · Nutrition Metabolism and Cardiovascular Diseases · doi:10.1016/j.numecd.2026.104862
Metadata
- Authors
- Zhao, Y., Zhuang, Z., Li, Y., Xiao, W., Song, Z., Huang, N., Wang, W., Dong, X., Jia, J., Clarke, R., & Huang, T.
- Affiliations
- Peking University (CN)
- University of Oxford (GB)
- Ministry of Education of the People's Republic of China (CN)
- Corresponding author
- Huang, Tao
- ORCID
- Venue
- Nature Communications
- Published
- 2024-03-19
- Volume
- 15
- Issue
- 1
- Pages
- 2451-2451
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC10951224
- OpenAlex
- W4392954776
- Cited by
- 117
- References
- 53
- Citations by year
- 2026: 52 · 2025: 47 · 2024: 17
- FWCI
- 38.20
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82173499, 82204026)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Epidemiology › Chronic Disease Management Strategies
- Keywords
- remnant cholesterol, triglycerides, cardiometabolic multimorbidity, type 2 diabetes, ischemic heart disease, stroke, triglyceride-rich lipoproteins, disease progression, multi-state models, Mendelian randomization, genetic instruments, causal inference
- MeSH terms
- Multimorbidity, Cholesterol, Diabetes Mellitus, Type 2, Humans, Hypercholesterolemia, Risk Factors, Triglycerides, Myocardial Ischemia
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